tbuckley/cabot-search huggingface dataset:
POS0793 IMPROVED RELAPSE-FREE SURVIVAL WITH THE NORWICH PREDNISOLONE REGIMEN FOR GIANT CELL ARTERITIS
Authors: G. Ducker, K. Mills, C. Yong, C. Jones, C. Mukhtyar
Journal: Annals of the Rheumatic Diseases (2022)

Background Glucocorticoid therapy is the mainstay treatment for GCA. There is no consensus on the dose of prednisolone to be used. Prednisolone regimens used in clinical trials have reported relapse rates of 66 to 92%. The long-term follow-up of Tocilizumab and prednisolone for 1-year showed a relapse rate of 74% at 2 years. The Norwich Regimen is a bespoke prednisolone plan with an initial dose of 1mg/kg of lean body mass. It delivers 164.64 mg/kg of lean body mass in a logarithmic taper over 100 weeks. It was devised to reduce the risk of relapse and allow patients to be in control of their prednisolone reduction. Objectives To document drug-free survival at 150 weeks of people with GCA treated with a bespoke prednisolone taper Methods All patients were diagnosed by biopsy, ultrasonography or PET scan and provided with a printed prednisolone plan at diagnosis. All individuals were assessed at approximately 3-6 monthly intervals in addition to suspected relapse, toxicity or other need for course correction. Relapses were confirmed objectively using a modification of the Kerr criteria. Relapse free survival was recorded at 100 weeks. Patients were given an open invite to contact us in the event of a suspected relapse after coming off prednisolone. A notes review was done to record events at 150 weeks. Results 150 consecutive people with objectively diagnosed GCA (mean age 74) since 10/01/2012 have completed 150 weeks since starting prednisolone. Drug-free, relapse-free survival at 100 weeks was met by 133/150 (89%). 7 individuals died and 20 relapsed. A further 5 died and 15 relapsed by week 150; 103/150 (69%) survivors were in prednisolone-free remission. Of the 12 deaths – 6 died of cancer, 1 subdural haemorrhage, 1 ischaemic bowel, 1 septicaemia, 1 general decline (aged 93). The cause of death was not available for 2 individuals who died in the community. The median time to relapse for the 35 individuals was 80 weeks (IQR 64,109). Conclusion We report the first results of a bespoke prednisolone taper to be used in real life. The Norwich Regimen for the treatment of GCA results in drug-free relapse-free survival of 89% at 100 weeks and 69% at 150 weeks, which is superior to all other reports published so far. References [1]Mukhtyar, C, Cate, H, Graham, C, Merry, P, Mills, K, and Misra, A, 2019, ‘Development of an evidence-based regimen of prednisolone to treat giant cell arteritis – the Norwich regimen’ Rheumatology Advances in Practice, Volume 3, Issue 1, 2019, rkz001, https://doi.org/10.1093/rap/rkz001 [2]Hellmich B, Agueda A, Monti S, et al2018 Update of the EULAR recommendations for the management of large vessel vasculitis Annals of the Rheumatic Diseases 2020;79:19-30. Disclosure of Interests None declared
AB0193 BIOLOGIC DRUGS RETENTION IN ELDERLY RHEUMATOID ARTHRITIS: WHAT FEATURES?
Authors: S. Boussaid, K. Saadaoui, S. Jemmali, M. Hassayoun, S. Rekik, S. Rahmouni, H. Sahli, M. Elleuch
Journal: Annals of the Rheumatic Diseases (2022)

Background The elderly RA population is expanding. The management of RA in elderly patients can be challenging because of comorbidities, the frequency of adverse events. The efficacy and safety of RA therapies; particularly biologics drugs (bDMARDs); are poorly studied in this age group. Objectives To investigate the therapeutic response to bDMARDs in elderly rheumatoid arthritis. Methods We conducted a cross-sectional and observational study. Files of patients with RA on biologics drugs (archived from the files of patients on the National Health Insurance Fund of Tunis) were studied. The characteristics of RA, and the current treatments were studied. We have divided our population into two age groups. G1 aging under 65 years and G2 aged 65 or over. The therapeutic maintenance rate as well as the biologics survival was analyzed using Kaplan-Meier survival curves and compared using the Log-Rank test. Results Three hundred and seventy-four files were selected. Their average age was 55±12.54 years [20-90]. A female predominance was noted with a sex ratio M/F=0.147. The average duration of RA was 11.7±6.76 years [2-41]. Subjects over the age of 65 represented 22.2% of the workforce, i.e. 83 patients. The first biotherapy prescribed was etanercept in 54% of cases, adalimumab in 14% of cases, certolizumab pegol 13%, infliximab 6%, tocilizumab 6% and rituximab in 7% of cases. The 4-year survival was 54.41% and 60.94% for subjects under 65 and 65 or older, respectively. Treatment maintenance for RA in the elderly (≥ 65 years old) was 42.21 months, [53.51–46.92]. In our study, age did not influence the survival of biologics with a Hazard Ratio (HR) = 0.997 (p=0.667). Conclusion RA therapy is generally effective and safe in elderly patients. We did not find any influence of age on survival and therapeutic maintenance of biological treatments. Further studies with a broader spectrum are needed to better understand this notion Disclosure of Interests None declared
AB0046 RESISTANCE TO OXIDATIVE DEGRADATION OF A FORMULATION COMBINING HYALURONIC ACID AND NIACINAMIDE
Authors: F. Hadjab
Journal: Annals of the Rheumatic Diseases (2022)

Background Hyaluronic acid plays a major role in the homeostasis of cartilage. In cases of osteoarthritis, hyaluronic acid is subjected to significant oxidative stress linked to the inflammation cascade leading to drastic diminution of its quantity at the level of the joint. This decrease in hyaluronic acid reduces dramatically the lubricating properties of the synovial fluid. Several preparation methods have been developed to further stabilize the hyaluronic acid used as viscosupplement such as crosslinking or adding adjuvants. Objectives A new formulation intended for intra-articular administration has been developed consisting of a combination of hyaluronic acid and vitamin B3 commonly called Niacinamide. The addition of niacinamide has a protective effect against hyaluronic acid under heat stress and under oxidative stress. Methods In order to assess the resistance to free radicals, 4 products were compared (HA 2.2%+vitamin B3 vs HA at 2.2% vs 2 cross-linked HA). 1 gram of sample were placed on Peltier Plate of a Rheometer – TA instrument and submitted to a temperature of 37°C. 50µL of H2O2 was introduced on the sample. The rheological properties of the mixture were followed-up at a shear stress of 1Hz until full degradation of the sample (i.e. until reaching a viscosity close 0). The degradation was calculated at each time point and plotted on a graph to compare the enzymatic degradation kinetics. To assess the thermal resistance, 2 products were compared (HA 2.2%+ vitamin B3 vs HA 2.2%). The samples consisting of 2 grams of gel packaged in glass syringe were placed in a dry oven at 50°C. The viscosity was measured at 3 different timepoints. Results This study demonstrates a significant better resistance to free-radical degradation for the HA+Niacinamide vs comparative products. The viscosity follow-up under heat stress demonstrated that the adjunction of Niacinamide does have a positive effect in preserving the HA viscosity consistently throughout time. Conclusion Vitamin B3 commonly called Niacinamide exhibits a dual positive effect when associated with Hyaluronic Acid. The study demonstrates a better resistance to oxidative degradation for the HA+Niacinamide most probably due to the antioxidant effect of Niacinamide. This study confirmed the adjunction of the Niacinamide into the HA-based gel formulation does increase the stability of HA against thermal degradation. References Data on file Disclosure of Interests Farid HADJAB Consultant of: Albomed GmbH, Grant/research support from: Albomed GmbH
AB0609 Gaps in the diagnosis of Takayasu Arteritis: a Romanian cohort
Authors: A. Predoiu, C. Pamfil, I. Felea, L. Muntean, L. Damian, M. M. Tamas, I. Filipescu, S. P. Simon, S. Rednic
Journal: Annals of the Rheumatic Diseases (2022)

Background The diagnosis of Takayasu arteritis still represents a big challenge, even though the disease was first described more than 100 years ago. Proof of that is the continuing effort to develop criteria with high specificity and sensitivity. 1 Objectives The aim of the study was to describe the clinical and paraclinical aspects of the disease at the time of diagnosis. Additionally, we wanted to evaluate the damage score in view of the diagnosis delay. Methods We retrospectively studied the clinical chart of 17 consecutive patients admitted to the Rheumatology Clinic of Emergency County Hospital from Cluj-Napoca, Romania between 2003 and 2021. Results There was just one man in the cohort (0.05%). The average age at the time of diagnosis was 37.5 years old. The average delay in the diagnosis was 33 months, while the biggest delay was of 240 months. The diagnosis was made by rheumatologists in 58% of the cases, while 29% by cardiologists and 11.7% by internal medicine specialists. The most frequent symptoms were limb claudication (64.7%), fatigue (52.9%) and headache (52.9%). Vascular bruits were found in most of the patients at the time of diagnosis (70.5%), as well as blood pressure and pulse difference between arms (52.9%). Unobtainable blood pressure was seen in 5 patients (29.4%). There was a discrepancy in 3 patients (17.6%) between inflammatory markers and inflammation in the vessels’ walls, as confirmed by imaging techniques (angioMRI or angioCT). Most of the patients were classified as type V arteritis (35%), followed by type IV (18%), type I (17%), type IIA, respectively type IIB (12% each) and type III (6%). Stenosis of the involved arteries occurred 4.3 times more than aneurysm formation. Eight patients required vascular interventions at the time of diagnosis – four were treated by balloon angioplasty and six by stent placing. The average TADS (Takayasu Arteritis Damage Score) was 1.5 and it was not associated with delay in diagnosis (p&gt;0.05). Conclusion Takayasu arteritis is a disease with heterogenous and nonspecific symptoms. For those reasons the delay in diagnosis is usually long, the treatment is started late and damage appears early in the course of the disease. This is reflected by the high amounts of vascular procedures needed at the time of diagnosis. We need better diagnostic criteria and specific monitoring scores. References [1]Keser G, Aksu K. Diagnosis and differential diagnosis of large-vessel vasculitides. Rheumatol Int. 2019;39(2):169-185. Disclosure of Interests None declared
POS1488-HPR DETERMINANTS OF PATIENT AND PHYSICIAN GLOBAL ASSESSMENT OF DISEASE ACTIVITY IN LARGE VESSEL VASCULITIS.
Authors: A. Kernder, M. Rohde, H. Acar, O. Sander, J. Richter, R. Fischer-Betz, M. Schneider, G. Chehab
Journal: Annals of the Rheumatic Diseases (2022)

Background Factors influencing disease activity assessment by patients and physicians are unknown, but are highly relevant in the context of PROs development. Objectives To compare the patients’ and physicians’ global assessment of disease activity in large vessel vasculitis and investigate factors influencing the assessment of disease activity. Methods Between 2010 and 2020, patients with large vessel vasculitis and their routine caring physicians assessed a global disease activity score (numerical rating scale 0 – 10) in our outpatient clinic. We compared these global scores of disease activity. In a multiple linear regression analysis we examined the influence of potential demographical and clinical factors on the disease activity assessment. Results 138 Patients with 866 assessments were available for analysis. At timepoint of assessment they had a mean age of 76 (± 9) years and a mean disease duration of 5 years (± 5). The median global score of patient-reported disease activity was 3 points, the median physicians’ disease activity assessment was 2 points. In 28,2% (n=244) there was a deviation of more than 2 points between the patients’ and physicians’ assessment of disease activity. Only 5 times the physicians, but 232 times the patients rated their disease activity higher than 5 points. In this group the patient-reported disease activity was associated with the patients age (β 0.025), the patients BMI (β 0.071) and the extent of pain (β 0.19), p&lt;0.05. The disease duration, CRP level and the psychological well-being of the patient showed no association. Conclusion In our cohort, physicians and patients showed greater divergence in disease activity assessment with higher disease activity. Age, BMI and the extent of pain were associated with higher disease activity ratings by the patients. This results are relevant for the development and interpretation of PROs for activity assessment in large vessel vasculitides. Disclosure of Interests Anna Kernder: None declared, Marius Rohde: None declared, Hasan Acar: None declared, Oliver Sander Speakers bureau: SOBI Pharma, EUSA Pharma, AbbVie Pharma, Consultant of: SOBI Pharma, EUSA Pharma, Boehringer Pharma, Jutta Richter: None declared, Rebecca Fischer-Betz: None declared, Matthias Schneider Speakers bureau: Astra-Zeneca; Biogen; BMS; Celgene; Chugai; GSK; Janssen-Cilag; Lilly; Pfizer; UCB, Paid instructor for: Lilly, Consultant of: Abbvie; Astra-Zeneca; Boehringer-Ingelheim; GSK; Lilly; Novartis; Pfizer; Protagen; Roche; Sanofi-Aventis; UCB, Grant/research support from: Abbvie; Astra-Zeneca; GSK; UCB, Gamal Chehab: None declared
AB0580 BEHÇET’S DISEASE IN OSLO NORWAY IN PERIOD 1999 – 2021
Authors: J. L. Lorentsen, K. Lerang, T. Garen, Ø. Palm
Journal: Annals of the Rheumatic Diseases (2022)

Background Bechet’s disease (BD) is a multisystemic, inflammatory disease, characterized by variety of clinical manifestations, including mucocutaneous, ocular, vascular, neurological (CNS) and gastrointestinal (GI) involvements. The disease can be seen at any age and occurs across gender, ethnic groups, and geographical areas. However, there are only a few studies from northern Europe. Objectives To study the demographics and clinical feature of patients with Bechet’s disease (BD) in Oslo Norway. Methods In this retrospective study we reviewed hospital records from Oslo University Hospital (OUS), a referral hospital for systemic inflammatory vasculitis in Norway. All patients living in Oslo with ICD-10 code M35.2 were identified, and their BD-related data recorded. Those fulfilling either the International Study Group criteria (ISG) or International Criteria for Bechet’s disease (ICBD) were included. Patients were defined as non-Norwegian when none of the parents was of Norwegian ancestry. The differences between groups were compared by Chi-square test using the Statistical Package for the Social Sciences (SPSS). Results We identified a total of 58 patients fulfilling the inclusion criteria (Table 1). Among them, 30 (52%) were females and 25 (43%) of Norwegian ancestry. Mean age at onset was 26 years, and at diagnosis 32 years. Table 1. Demographics of Behcet`s patients in Oslo Norway Counts (%) Norwegian ancestry Non-Norwegian ancestry All (%) All (%) 25 (43) 33 (57) 58 (100) Male (%) 8 (29) 20 (71) 28 (48) Female (%) 17 (57) 13 (43) 30 (52) ISG Criteria (%) 20 (47) 23 (53) 43 (100) ICBD Criteria (%) 25 (43) 33 (57) 58 (100) Age at diagnosis mean (SD) years 33 (11.85) 32 (9.36) 32 (10.41) Age at onset mean (SD) years 24 (9.34) 27 (9.52) 26 (9.42) The most prevalent clinical manifestations were oral ulcers (n=58, 100%), genital ulcers (n=49, 84%) and skin lesions (n=40, 69%). Ophthalmic complications (n=21, 36%), arthritis (n=20, 34%), vascular involvement (n=7, 12%), CNS (n=3, 5%) and gastrointestinal (GI) complications (n= 4, 7%) were also present. There was no significant difference of clinical features between patients with Norwegian ancestry and those with non-Norwegian ancestry (data not shown). Figure 1. Conclusion BD was most prevalent among patients of non-Norwegian ancestry. We found a wide spectrum of clinical manifestations occurring during the disease course. Mucocutaneous lesions were most frequent, but potential serious manifestations were also present. These manifestations were similarly distributed between patients with Norwegian and non-Norwegian ancestry (Figure 1). References [1]Davatchi F. et al. Behcet`s disease: epidemiology, clinical manifestations and diagnosis. Expert Review of Clinical Immunology, 13:1, 57-65, DOI: 10.1080/1744666X.2016.1205486 Disclosure of Interests None declared
POS1193 COVID-19 IN PATIENTS WITH GIANT CELL ARTERITIS
Authors: J. Kramarič, R. Jese, M. Tomsic, Z. Rotar, A. Hočevar
Journal: Annals of the Rheumatic Diseases (2022)

Background Patients with giant cell arteritis (GCA) represent a fragile population with an increased infection risk. In a recent study 1 older age, a higher number of comorbidities, higher disease activity, and prednisolone ≥10 mg qd were associated with worse COVID-19 outcomes. Objectives We aimed to evaluate the frequency and severity of COVID-19 in a well-defined GCA cohort. Methods We reviewed medical records of histologically and/or by imaging proven GCA patients diagnosed between September 2011 and February 2020 at our secondary/tertiary center and followed during the COVID-19 pandemic between March 2020 and December 2021 (22 months). Descriptive statistics was used to analyze the studied population. Results Of 314 GCA patients diagnosed for the first time during a 102-month period, 49 patients died before March 2020. Of the remaining 265 patients (69.4% females), SARS-CoV-2 infection was proven by PCR test in 39 (14.7%) patients (74.2% females, mean (SD) age at infection 76.2 (±9.6 years), 13 (33.3%) with large vessel GCA and 16 with cranial limited GCA). At the time of SARS-Cov-2 infection GCA was in a stable remission in 38 patients (13 without therapy, 10 on steroids alone, 9 on leflunomide monotherapy, 6 on steroids plus leflunomide (10 or 20 mg qd), 1 on ustekinumab; mean prednisolone equivalent dose of 4.6 mg qd) and relapsed in one patient 6 weeks earlier (prednisolone 30 mg plus leflunomide). Data on clinical manifestations of COVID-19 were available for 33 (84.6%) patients and are presented in Table 1, part A. Twenty-nine/39 (74.4%) patients had mild COVID-19 and were symptomatically treated at home, while 10 patients had severe infection (defined as a need of hospitalization and/or death), and one of those patients died due to COVID-19. One patient developed a transient neurologic ischemic attack related to COVID-19. Table 1, part B shows differences in GCA demographic and treatment at the time of mild vs. severe infection. We found no differences in gender, age, GCA type and GCA treatment between those with mild vs. severe COVID. Three patients developed COVID-19 after receiving two doses of anti-COVID vaccine (1.4% breakthrough rate). Overall, of 257 GCA patients eligible for vaccination, 210 (81.7%) were vaccinated by the end of December 2021. Conclusion A quarter of our GCA patients had severe COVID-19. Low doses of glucocorticoids and treatment with leflunomide were not associated with severe COVID-19 course in our cohort. References [1]Sattui SE, et al. Lancet Rheumatol 2021; doi: 10.1016/S2665-9913(21)00316-7 Disclosure of Interests None declared
POS0399 CHARACTERIZATION OF HSP60, A STROMAL-DERIVED AUTOANTIGEN, RECOGNIZED BY RA SYNOVIAL RECOMBINANT MONOCLONAL ANTIBODIES
Authors: E. Corsiero, M. Caliste, L. Jagemann, E. Prediletto, C. Pitzalis, M. Bombardieri
Journal: Annals of the Rheumatic Diseases (2022)

Background Up to 50% of rheumatoid arthritis (RA) patients display synovial ectopic lymphoid structures (ELS) supporting B-cell autoreactivity toward locally generated citrullinated and other translationally modified antigens. Recently, screening a large number of recombinant monoclonal antibodies (rmAbs, n=71) which we derived from locally differentiated B-cells from RA ELS+ synovium [1], we identified a subset of antibodies which specifically recognise fibroblast-like-synoviocytes (FLS) (10 out of 71), suggesting FLS as a cellular source of autoantigens fuelling the local autoimmune response. We reported that calreticulin is one of the antigenic targets of these anti-FLS rmAbs, while the nature of other FLS-derived autoantigens is still unclear [2]. Objectives Here we aimed to define other stromal-derived autoantigens from RA-FLS targeted by RA-rmAbs. Methods Western blotting/mass-spectrometry were used to identify potential autoantigens from RA-FLS protein extracts. Putative candidates were validated using colocalization immunofluorescence confocal microscopy/ELISA/immunoprecipitation assay. Finally, both serum and synovial fluid (SF) from RA patients (OA patients used as control) were tested for immunoreactivity towards the putative antigen. Results Following immunoprecipitation and mass-spectrometry analysis, among the anti-FLS antibodies we identified a subset of RA-rmAbs which display strong reactivity towards heat shock protein 60 (HSP60). Three RA-rmAbs confirmed a clear immunoreactivity towards HSP60 in ELISA assay in a dose-dependent manner. Confocal microscopy did not show co-localization between anti-HSP60 RA-rmAbs and HSP60, suggesting that HSP60 act as autoantigen when released from the RA-FLS in stress condition. Finally, anti-HSP60 Abs were preferentially detected in RA-SF versus OA-SF, with an accumulation of HSP60 in RA-SF versus RA sera. Conclusion Here, we identified synovial B cell-derived RA-rmAbs locally differentiated within the ELS+ RA synovium reacting toward HSP60, suggesting that FLS-derived HSP60 may contribute to fuel the local autoimmune response. Elucidating the mechanisms involved in RA-FLS activation in vitro/in vivo will be important to clarify the anti-FLS rmAbs functional role in modulating inflammation. References [1]Corsiero et al , ARD 2016; [2] Corsiero et al , JI 2018. Acknowledgements This work was supported by a research grant from Versus Arthritis (Grant 22440 to E. Corsiero). Disclosure of Interests None declared.
Storing and analyzing a genome on a blockchain
Authors: Gamze Gürsoy, Charlotte M. Brannon, Eric Ni, Sarah Wagner, Amol Khanna, Mark Gerstein
Journal: Genome biology (2022)

There are major efforts underway to make genome sequencing a routine part of clinical practice. A critical barrier to these is achieving practical solutions for data ownership and integrity. Blockchain provides solutions to these challenges in other realms, such as finance. However, its use in genomics is stymied due to the difficulty in storing large-scale data on-chain, slow transaction speeds, and limitations on querying. To overcome these roadblocks, we developed a private blockchain network to store genomic variants and reference-aligned reads on-chain. It uses nested database indexing with an accompanying tool suite to rapidly access and analyze the data.